中文摘要：

目的：研究葡萄籽原花青素（GSP）对糖尿病大鼠肾保护作用的分子生物学机制，为GSP治疗糖尿病肾病提供实验依据。方法：雄性Wistar大鼠尾静脉注射0．1％链脲佐菌素（STZ）建立糖尿病大鼠模型，成模后随机分为糖尿病组（DM组）和糖尿病GSP治疗组（GSP组，GSP250mg·kg-1·d-1），另设正常对照组（C组）。观察24周后测量大鼠体重、收缩压、肾重／体重和24h尿蛋白定量；采血测定空腹血糖（FPG）、尿素氮（BUN）、肌酐（SCr）和糖基化血红蛋白（HbAlc）；观察糖尿病大鼠肾脏病理改变，并应用Westernblotting和免疫组化法测定肾组织谷胱甘肽S-转移酶μ亚型（GSTM）和核因子E2相关因子2（Nrf2）的表达。结果：实验开始时3组大鼠体重无明显差异（P〉0．05），24周时DM组大鼠较C组大鼠体重显著下降（P〈0．01），治疗后GSP组大鼠体重较DM组增加，但无显著差异（P〉0．05）。第24周时DM组大鼠与C组相比较，收缩压、FPG、HbAlc、肾重／体重、24h尿蛋白定量、BUN和SCr水平显著升高（P〈0．01）。治疗后GSP组大鼠与DM组比较FPG和HbAlc水平降低，但无显著差异（P〉0．05），收缩压、24h尿蛋白定量和肾重／体重显著降低，（P〈0．01），BUN和SCr水平显著降低（P〈0．05）。GSP组肾组织病理改变较DM组改善。GSTM和Nrf2表达在DM组表达较C组上调，在GSP组治疗后回调（P〈0．05）。结论：GSP可能通过Nrf2下调GSTM表达而起肾保护作用。

英文摘要：

AIM： To investigate the potential mechanisms of renoprotective effect of grape seed proanthocyanidin （GSP） on diabetic nephropathy. METHODS： Male Wistar rats were injected with 1% streptozotocin （STZ） intravenously to induce diabetes mellitus （DM）. The diabetic rats were randomly divided into 2 groups： diabetes group （DM group） and GSP treatment group （GSP group, GSP 250 mg·kg-1·d-1）. The normal Wistar rats served as control （C group）. Body weight （BW）, systolic pressure, kidney weight/body weight （KW/BW）, fasting plasma glucose （FPG）, blood urea nitrogen （BUN）, serum creatinine （SCr）, glycosylated hemoglobin （HbAlc） and 24 h urine protein were determined 24 weeks after STZ intervention. The pathological changes of the renal tissues were observed. The protein levels of glutathione S - transferase mu （GSTM） and nuclear factor - erythroid 2 - related factor 2 （Nrf2） in the renal tissues were determined by Western blotting and immunohistochemistry. RESULTS： Compared with C group, BW in diabetic rats decreased （P 〈 0.01 ）. The levels of systolic pressure, FPG, HbAI c, KW/BW, 24 h urine protein, BUN and SCr in DM group were higher than those in C group （P 〈 0.01 ）. After treated with GSP, the levels of systolic pressure, KW/BW, 24 h urine protein, BUN and SCr in DM rats were lower than those in DM rats without treatment （P 〈0. 01 or P 〈0. 05）. The pathological changes were ameliorated in GSP group. The expression of GSTM and NrF2 was up - regulated in the kidneys of diabetic rats and down - regulated to the normal levels after GSP treatment. CONCLUSION ： The renoprotective effect of GSP is associated with the down - regulation of GSTM through modulating the expression of Nrf2.